Reaction mass of 2-[[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]methyl]oxirane and 1,3-bis[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]propan-2-ol and 1-[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]-3-[4-[[4-[3-[4-[[3,5-dimethyl-4-(oxiran-2-ylmethoxy)phenyl]methyl]-2,6-dimethyl-phenoxy]-2-hydroxy-propoxy]-3,5-dimethyl-phenyl]methyl]-2,6-dimethyl-phenoxy]propan-2-ol

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Young adult animals (approx. 10 weeks old)
- Weight at study initiation: variation was within ± 20% of the sex mean.
- Housing: Group housed
- Diet (e.g. ad libitum): ad libitum to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water (e.g. ad libitum): Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 24°C
- Humidity (%):40 to 70%
- Air changes (per hr):approximately 10 room air changes/hour
- Photoperiod (hrs dark / hrs light):12-hour light/12-hour dark cycle.

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

0, 10, 25 and 50 % (test substance w/w)

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS:
- Two test substance concentrations were tested; a 25% and 50% concentration. The highest concentration was the maximum concentration as
required in the test guidelines (50% for solids).
- Irritation: No irritation and no signs of systemic toxicity were observed in any of the animals examined.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (1 per day)
- Exposure period: Days 1-3
- Test groups: 2,3,4
- Control group: 1
- Site: Dorsal surface of both ears (25 uL/ear)
- Frequency of applications: Once per day (Each ear) at approximately the same time each day
- Concentrations: 0, 10, 25 or 50% (test substance w/w)
- Exision of the nodes was undertaken on Day 6.
Each animal was injected via the tail vein with 0.25 mL of sterile phosphate buffered saline (PBS) (Merck, Darmstadt, Germany) containing 20 μCi of
3H-methyl thymidine (PerkinElmer Life and Analytical Sciences, Boston, MA, US). After approximately 5 hours animals were killed and the nodes
excised.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Statistics:

Statistical analysis not conducted, as not a requiement of the guideline.

Positive control results:

The SI values calculated for the substance concentrations 5, 10 and 25% were 1.2, 1.4 and 4.7 respectively. An EC3 value of 9.8% was calculated
using linear interpolation. The calculated EC3 value was found to be in the acceptable range of 4.8 and 19.5%. .
Based on the results, it was concluded that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing
for contact hypersensitivity.

Parameter:

SI

Value:

3.8

Test group / Remarks:

10%

Parameter:

SI

Value:

10.4

Test group / Remarks:

25%

Parameter:

SI

Value:

18.8

Test group / Remarks:

50%

Parameter:

other: disintegrations per minute (DPM)

Value:

>= 793 - <= 14 941

Test group / Remarks:

0%: 793 ± 77 10%: 3004 ± 353 25%: 8266 ± 1725 50%: 14941 ± 3700

Interpretation of results:

sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The results indicate that the test substance could elicit an SI >/= 3. The data showed a dose response and the EC3 value was established to be between 0 and 10%. The test substance is a contact skin sensitiser

Based on the results, the test substance would be classified as a skin irritant category 1 according to the CLP regulation (EC) No 1272/2008, as amended.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The results indicate that the test substance could elicit an SI >/= 3. The data showed a dose response and the EC3 value was established to be between 0 and 10%.

Based on the results, the test substance would be classified as a skin irritant category 1 according to the CLP regulation (EC) No 1272/2008, as amended.

Migrated from Short description of key information:
Sensitisation potential was evaluated by a mouse Local Lymph Node Assay (LLNA)

Justification for selection of skin sensitisation endpoint:
The results indicated that the test substance elicited an SI >/= 3.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results indicate that the test substance could elicit an SI >/= 3. The data showed a dose response and the EC3 value was established to be between 0 and 10%.

Based on the results, the test substance would be classified as a skin irritant category 1 according to the CLP regulation (EC) No 1272/2008, as amended.